Accumulation of Multipotent Hematopoietic Progenitors in Peripheral Lymphoid Organs of Mice Over-expressing Interleukin-7 and Flt3-Ligand

Interleukin-7 (IL-7) and Flt3-ligand (FL) are two cytokines important for the generation of B cells, as manifested by the impaired B cell development in mice deficient for either cytokine or their respective receptors and by the complete block in B cell differentiation in the absence of both cytokines. IL-7 is an important survival and proliferation factor for B cell progenitors, whereas FL acts on several early developmental stages, prior to B cell commitment. We have generated mice constitutively over-expressing both IL-7 and FL. These double transgenic mice develop splenomegaly and lymphadenopathy characterized by tremendously enlarged lymph nodes even in young animals. Lymphoid, myeloid and dendritic cell numbers are increased compared to mice over-expressing either of the two cytokines alone and the effect on their expansion is synergistic, rather than additive. B cell progenitors, early progenitors with myeloid and lymphoid potential (EPLM), common lymphoid progenitors (CLP) and lineage−, Sca1+, kit+ (LSK) cells are all increased not only in the bone marrow but also in peripheral blood, spleen and even lymph nodes. When transplanted into irradiated wild-type mice, lymph node cells show long-term multilineage reconstitution, further confirming the presence of functional hematopoietic progenitors therein. Our double transgenic mouse model shows that sustained and combined over-expression of IL-7 and FL leads to a massive expansion of most bone marrow hematopoietic progenitors and to their associated presence in peripheral lymphoid organs where they reside and potentially differentiate further, thus leading to the synergistic increase in mature lymphoid and myeloid cell numbers. The present study provides further in vivo evidence for the concerted action of IL-7 and FL on lymphopoiesis and suggests that extramedullary niches, including those in lymph nodes, can support the survival and maintenance of hematopoietic progenitors that under physiological conditions develop exclusively in the bone marrow

Notch1 mediates stage-specific dynamic transcriptional networks during early T-cell development

Notch1 signaling is essential to initiate and sustain T-cell development from early thymic progenitors (ETPs) to pre-T cells. How Notch orchestrates T cell lineage commitment remains an open question. Integrating multi-omics platforms of bulk RNA-Seq, ChIP-Seq, mass spectrometry, and HiC we identified 46 transcription factors (TFs) regulated by Notch1 via super-enhancers that mediate stage-specific transcriptional networks progressively during T cell commitment. Six of these TFs form a supramolecular complex with Notch1. Among those, ERG and FLI1 are essential very early, and the lack of both impaired the attenuation of stem cell and lineage programs. Ultimately, this led to conflicting transcriptional programs, hastened T-cell development, and apoptosis, emphasizing the importance of progressive acquisition of T cell identity

NMR and NQR study of the tetrahedral frustrated quantum spin system Cu2Te2O5Br2 in its paramagnetic phase

The quantum antiferromagnet Cu2Te2O5Br2 was investigated by NMR and nuclear quadrupole resonance (NQR). The Te-125 NMR investigation showed that there is a magnetic transition around 10.5 K at 9 T, in agreement with previous studies. From the divergence of the spin-lattice relaxation rate, we ruled out the possibility that the transition could be governed by a one-dimensional divergence of the spin-spin correlation function. The observed anisotropy of the Te-125 shift was shown to be due to a spin polarization of the 5s(2) "E" doublet of the [TeO3E] tetrahedra, highlighting the importance of tellurium in the exchange paths. In the paramagnetic state, Br NQR and NMR measurements led to the determination of the Br hyperfine coupling and the electric field gradient tensor, and to the spin polarization of Br p orbitals. The results demonstrate the crucial role of bromine in the interaction paths between Cu spins

Esophageal Mobilization in the Treatment of Short Esophagus

Short esophagus is well known complication of a long term gastroesophageal disease. There are several ways to solve this problem intraoperatively. One of the first steps is extensive esophageal mobilisation. In this review we emphasize different approaches and types of this procedure, with their advantages and disadvantages

Diverse expression of IL-32 in diffuse and intestinal types of gastric cancer

Copyright © 2018 Mladen Pavlovic et al. Introduction. Gastric cancer (GC) represents one of the most common cancers worldwide, frequently diagnosed at advanced stages with poor prognosis, indicating on need for new diagnostic and prognostic markers. The aim of the study was to determine the expression of IL-32, proinflammatory and angiogenic mediators, in patients with diffuse and intestinal gastric cancer and the relationship with clinicopathological aspects. Material and Methods. The tissue samples of diffuse and intestinal types of tumor of 70 patients with gastric cancer were analyzed. Expression of IL-32, VEGF, IL-17, and CD31 was measured by immunohistochemistry. Results. IL-32 expression was significantly lower in tissue samples from patients with diffuse type of gastric cancer that is also a severe and more progressive form (TNM stages III and IV, poor histological differentiation, and higher nuclear grade III). Expression of IL-17 was also decreased in patients with diffuse type of gastric cancer. Microvascular density was diminished in diffuse type of gastric cancer. Conclusions. Downregulated expression of IL-32 in tumor tissue of patients with diffuse type of gastric cancer may implicate on its role in limiting ongoing proinflammatory and proangiogenic processes. This emphasizes on unrecognized role of IL-32 in biology of diffuse type of gastric cancer